Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing, China.
Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Nutr Cancer. 2024;76(5):432-441. doi: 10.1080/01635581.2024.2324504. Epub 2024 Mar 5.
Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways.
We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed.
The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly.
In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC.HighlightsThe current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention.The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiotaOur results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.
观察性研究表明，饮食和药物会影响膀胱癌（BC）的发展，但这些研究受到混杂因素的影响，难以得出因果关系的结论。本研究旨在探讨这些观察性关联是否具有因果关系，并确定潜在的方向和途径。
我们使用两样本 Mendelian 随机化（MR）分析来评估饮食摄入、药物使用和分子与 BC 风险的关联。遗传汇总数据来自主要为欧洲血统的参与者，使用严格的仪器选择，进行了单变量 MR、中介 MR 和多变量 MR 分析。
单变量 MR 的结果表明，4 种饮食摄入和 4 种药物使用对 BC 具有保护作用，而 4 种循环代谢物、440 种循环蛋白和 2 种肠道微生物与 BC 风险存在因果关系。通过中介 MR，我们发现 572 种分析物在饮食摄入或药物使用与 BC 风险之间表现出一致的中介作用。此外，16 对饮食-药物组合中有 9 对在联合使用时对 BC 表现出显著的相互作用和改变。
综上所述，本研究的结果对于制定预防策略具有重要意义，这些策略指出了潜在的生活方式干预或药物处方，以降低患 BC 的风险。
本研究扩展了观察性文献，表明饮食和药物对膀胱癌预防的重要性。饮食和药物对膀胱癌预防的作用可能是通过循环代谢物、循环蛋白和肠道微生物实现的。我们的研究结果提供了对某些饮食-药物组合相互作用的新认识，医生和患者在制定治疗策略时应考虑到这一点。
